Nitrogen monoxide (NO) regulates numerous physiological processes, inter alia neurotransmission, the relaxation and proliferation of smooth muscle, the adhesion and aggregation of thrombocytes as well as tissue injury and inflammation. Due to the large number of signal functions, nitrogen monoxide has been associated with a series of diseases, for example in L. J. Ignarro, Angew. Chem. (1999), 111, pages 2002-2013 and in F. Murad, Angew. Chem. Int. Ed. (1999), 111, pages 1976-1989. Nitrogen monoxide synthase (NO synthase), the enzyme responsible for the physiological formation of nitrogen monoxide, plays an important role in influencing these diseases therapeutically. To date, three different isoforms of NO synthase have been identified, namely the two constitutive forms nNO synthase and eNO synthase together with the inducible form iNO synthase (A. J. Hobbs, A. Higgs, S. Moncada, Annu. Rev. Pharmacol. Toxicol. (1999), 39, pages 191-220; I. C. Green, P.-E. Chabrier, DDT (1999), 4, pages 47-49; P.-E. Chabrier et al., Cell. Mol. Life Sci. (1999), 55, pages 1029-1035).
The inhibition of NO synthase opens up new therapeutic approaches for various diseases which are associated with nitrogen monoxide (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, pages 191-220; I. C. Green, P.-E. Chabrier, DDT (1999), 4, pages 47-49; P.-E. Chabrier et al., Cell. Mol. Life Sci. (1999), 55, pages 1029-1035), such as for example migraine (L. L. Thomsen, J. Olesen, Clinical Neuroscience (1998), 5, pages 28-33; L. H. Lassen et al., The Lancet (1997), 349, 401-402), septic shock, neurodegenerative diseases such as multiple sclerosis, Parkinson's disease, Alzheimer's disease or Huntington's chorea, inflammation, inflammatory pain, cerebral ischaemia, diabetes, meningitis and arteriosclerosis. Inhibition of NO synthase may furthermore have an effect on wound healing, on tumours and on angiogenesis and bring about non-specific immunity towards microorganisms (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, pages 191-220).
Hitherto known active ingredients which inhibit NO synthase, apart from L-NMMA and L-NAME (i.e. L-arginine analogues from which nitrogen monoxide and citrulline are formed in vivo with the participation of NO synthase), are inter alia S-methyl-L-citrulline, aminoguanidine, S-methylisourea, 7-nitroindazole and 2-mercaptoethylguanidine (A. J. Hobbs et al., Annu. Rev. Pharmacol. Toxicol. (1999), 39, pages 191-220).